The Neo‐selectionist Theory of Genome Evolution


The role of chance in evolution is a central problem in biology, as illustrated, for instance, by Monod's book Chance and Necessity (1971). The present article will first sketch the classical evolutionary theories proposed since Darwin and the approaches used to study evolution, then focus on the recently proposed neo‐selectionist theory (Bernardi, 2007). At variance with the classical theories, the neo‐selectionist theory had its basis on observations made on the organization and the evolution of the eukaryotic genome, in particular of the vertebrate genome. This approach was started many years ago, but could recently take advantage of the availability of full genome sequences. Interestingly, the neo‐selectionist theory not only provides a solution to the neutralist/selectionist debate, but also introduces an epigenomic component in genome evolution.

Keywords: base composition; isochores; neo‐selectionist theory; nearly neutral theory; neutral theory

Figure 1.

Darwin postulated the existence of deleterious, advantageous and neutral changes. The neo‐Darwinians (or selectionists) neglected neutral changes. These were reintroduced and amplified by Kimura, who developed the neutral theory of evolution (a ‘non‐Darwinian evolution’ according to King and Jukes). The nearly neutral theory was proposed by Ohta to include intermediates between neutral and advantageous, as well as between neutral and deleterious changes. In the neo‐selectionist theory, the critical changes are responsible for the transition from point mutations to regional changes. Reproduced from Bernardi .

Figure 2.

Overview of isochores on 100 Mb of human chromosome 1. The isochores identified on the telomeric 100 Mb region of the short arm of chromosome 1 (as a representative region of human chromosomes) are shown. Broken horizontal guidelines in the top frames represent GC levels. Horizontal red stretches in the bottom frames represent isochores. The boundaries were identified mainly on the basis of GC jumps of adjacent isochores. The colour code ranges from ultramarine blue (GC‐poorest regions) to red (GC‐richest regions). Reproduced with permission from Costantini et al. .

Figure 3.

Distribution of isochores according to GC levels. The histogram shows the distribution (by weight) of isochores as pooled in bins of 1% GC. Colours represent isochore families as in Figure . Values at minima (histogram bars with mixed colours) were split between the two neighbouring families. The Gaussian profile shows the distribution of isochores. Reproduced with permission from Costantini et al. .

Figure 4.

DNA and gene distribution in the isochore families of the human genome. The major structural and functional properties associated with each gene space are listed (in blue for the genome desert and in red for the genome core). Reproduced from Bernardi .

Figure 5.

Scheme of the compositional evolution of vertebrate genomes. At the transition from cold‐ to warm‐blooded vertebrates, the gene‐dense, moderately GC‐rich ancestral genome core (pink box) became the gene‐dense, GC‐rich genome core (red box), whereas the GC‐poor and gene‐poor (blue box) genome desert did not undergo any major compositional change. This transitional (or shifting) mode, which was accompanied by an overall decrease of CpG doublets and mC (methylcytosine), was followed by a conservative mode of genome evolution in which compositional patterns were maintained. Reproduced from Bernardi .

Figure 6.

Time course of typical compositional changes of a GC‐rich region from a warm‐blooded vertebrate in the conservative mode of evolution. In an early phase, the average GC level of the region, initially visualized at its compositional optimum (arbitrarily set here at 54% GC), is decreasing because of the mutational AT bias (the vertical grey bars crossing the black DNA line represent the ‘excess’ GC→AT over AT→GC changes), but remains within a tolerated range (whose arbitrary thresholds are indicated by the thick horizontal broken lines). In a late phase, the average GC level trespasses the lower threshold (arbitrarily fixed here at 52% GC), because of the last changes, the critical changes. The chromatin (solid boxes) then undergoes a structural change (broken box) that is deleterious for transcription and replication (see text). Until then, the changes may be neutral or, more probably, nearly neutral. Reproduced from Bernardi .

Figure 7.

A scheme of the transitional mode of evolution describing the GC increase of a gene‐dense DNA region during the emergence of homeothermy. The basic feature is an increase in the GC level of the lower threshold (broken line) by a ratchet mechanism, which leads to an increased GC level of the region (pink to red lines). Reproduced from Bernardi .



Bernardi G and Bernardi G (1986) Compositional constraints and genome evolution. Journal of Molecular Evolution 24: 1–11.

Bernardi G (2007) The neo‐selectionist theory of genome evolution. Proceedings of the National Academy of Sciences of the USA 104: 8385–8390.

Costantini M and Bernardi G (2008) Replication timing, chromosomal bands and isochores. Proceedings of the National Academy of Sciences of the USA 105: 3433–3437.

Costantini M, Clay O, Auletta F and Bernardi G (2006) An isochore map of human chromosomes. Genome Research 16: 536–541.

Darwin C (1859; reprinted in 1964) On the Origin of Species. A Facsimile of the First Edition with an Introduction by Ernst Mayr. Cambridge, MA: Harvard University Press.

de Duve C (1995) Vital Dust: Life as a Cosmic Imperative. New York, NY: Basic Books.

Freese E (1962) On the evolution of base composition of DNA. Journal of Theoretical Biology 3: 82–101.

Kimura M (1968) Evolutionary rate at the molecular level. Nature 217: 624–626.

King JL and Jukes TH (1969) Non‐Darwinian evolution. Science 164: 788–798.

Monod J (1971) Chance and Necessity. New York: Alfred A. Knopf.

Ohta T (2002) Near‐neutrality in evolution of genes and gene regulation. Proceedings of the National Academy of Sciences of the USA 99: 16134–16137.

Sueoka N (1962) On the genetic basis of variation and heterogeneity of DNA base composition. Proceedings of the National Academy of Sciences of the USA 48: 582–592.

Zuckerkandl E and Pauling L (1962) Molecular disease, evolution, and genetic heterogeneity. In: Kasha M and Pullman B (eds) Horizons in Biochemistry, pp. 189–225. New York: New York Academic Press.

Further Reading

Bernardi G (2004, reprinted in 2005) Structural and Evolutionary Genomics. Natural Selection in Genome Evolution. Amsterdam: Elsevier.

Bernardi G (2008a) Evolutionary history of the human genome – updated version. In: Encyclopedia of Life Sciences. Chichester: Wiley.

Bernardi G (2008b) Genome organization of vertebrates – updated version. In: Encyclopedia of Life Sciences. Chichester: Wiley.

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Bernardi, Giorgio(Jul 2008) The Neo‐selectionist Theory of Genome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021002]